Hypertension is the cause of a variety of angiopathies, the degree and character of damage to the vessel wall reflecting the magnitude and duration of the blood pressure elevation. The microvasculature plays a fundamental role in the genesis and maintenance of the hypertension. The overall goal of the proposed research program is to delineate the basic microvascular alterations underlying the development and continuation of the hypertensive state. To gain insight into these fundamental processes, we propose to quantify the reactions of the microvascular wall with state-of-the-art microcirculatory techniques. To achieve our goal, we propose 3 series of experimental studies. The first series focuses on the mechanical properties of the hypertensive arteriole, with special emphasis on the elastic and contractile elements. Also the effects of vasoactive hormones (e.g. angiotensin) on the mechanics of the arteriolar wall will be analyzed. In the second series of experiments, the permeability of hypertensive arterioles, capillaries and venules will be quantified utilizing digital computer analysis of video images of the microvascular bed. In addition, the vulnerability of hypertensive endothelium to endogenous permeability-altering substances (e.g., histamine) will be studied. The biochemistry of arteriolar smooth muscle in the hypertensive state is the subject of the third series of experiments. Enzyme activities and substrate levels in the arteriolar wall will be quantified utilizing microspectrophotometric techniques. From these studies, we hope to gain new insights into the mechanisms, prevention and treatment of hypertension.